Abstract：
Diabetic nephropathy (DN) remains the primary cause of end-stage renal disease (ESRD), warranting equal attention and separate analysis of glomerular, tubular, and interstitial lesions in its diagnosis and intervention. This study aims to identify the specific proteomics characteristics of DN, and assess changes in the biological processes associated with DN. 5 patients with DN and 5 healthy kidney transplant donor control individuals were selected for analysis. The proteomic characteristics of glomeruli, renal tubules, and renal interstitial tissue obtained through laser capture microscopy (LCM) were studied using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Significantly, the expression of multiple heat shock proteins (HSPs), tubulins, and heterogeneous nuclear ribonucleoproteins (hnRNPs) in glomeruli and tubules was significantly reduced. Differentially expressed proteins (DEPs) in the glomerulus showed significant enrichment in pathways related to cell junctions and cell movement, including the regulation of actin cytoskeleton and tight junction. DEPs in renal tubules were significantly enriched in glucose metabolism-related pathways, such as glucose metabolism, glycolysis/gluconeogenesis, and the citric acid cycle. Moreover, the glycolysis/gluconeogenesis pathway was a co-enrichment pathway in both DN glomeruli and tubules. Notably, ACTB emerged as the most crucial protein in the protein-protein interaction (PPI) analysis of DEPs in both glomeruli and renal tubules. In this study, we delve into the unique proteomic characteristics of each sub-region of renal tissue. This enhances our understanding of the potential pathophysiological changes in DN, particularly the potential involvement of glycolysis metabolic disorder, glomerular cytoskeleton and cell junctions. These insights are crucial for further research into the identification of disease biomarkers and the pathogenesis of DN.
摘要：
糖尿病肾病（DN）仍然是终末期肾病（ESRD）的主要原因，保证对肾小球的同等关注和单独分析，管状,和间质病变的诊断和干预。本研究旨在明确DN的特异性蛋白质组学特征,并评估与DN相关的生物过程的变化。选择5例DN患者和5例健康肾移植供体对照个体进行分析。肾小球的蛋白质组学特征，肾小管,和通过激光捕获显微镜（LCM）获得的肾间质组织使用高效液相色谱-串联质谱（HPLC-MS/MS）进行研究。重要的是,多种热休克蛋白（HSPs）的表达，微管蛋白，肾小球和肾小管中的异质核核糖核蛋白（hnRNPs）显着减少。肾小球中的差异表达蛋白（DEPs）在与细胞连接和细胞运动相关的通路中显示出显著的富集，包括肌动蛋白细胞骨架和紧密连接的调节。肾小管中的DEP显著富集葡萄糖代谢相关通路,比如葡萄糖代谢，糖酵解/糖异生，和柠檬酸循环。此外，糖酵解/糖异生途径是DN肾小球和肾小管中的共富集途径。值得注意的是,ACTB是肾小球和肾小管中DEP的蛋白质-蛋白质相互作用（PPI）分析中最关键的蛋白质。在这项研究中,我们深入研究了肾组织每个亚区的独特蛋白质组学特征.这增强了我们对DN潜在病理生理变化的理解，特别是糖酵解代谢紊乱的潜在参与，肾小球细胞骨架和细胞连接。这些见解对于进一步研究疾病生物标志物的鉴定和DN的发病机制至关重要。
